CN108586407A - A kind of coumarin derivative and its preparation and application - Google Patents
A kind of coumarin derivative and its preparation and application Download PDFInfo
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Abstract
The invention discloses a kind of coumarin derivative and its preparations and application.Using 7 hydroxyl, 4 methylcoumarin as raw material, successively substitution reaction is carried out with halogen ethyl alcohol and 4 vinyl benzyl chlorides, up to 7 [2 (4 vinyl benzyl oxygroup) ethyoxyl] 4 methylcoumarins, this method has easy to operate, mild condition, product easy purification, the advantages that yield is high, the coumarin derivative of synthesis has polymerizable double bond primitive, alkoxy flexible spacer and cumarin photosensitive group, it is applied to the synthesis of light stimulus responsive polymer material as photosensitive monomer, polymerization efficiency can be significantly improved, and the water solubility of the polymer material synthesized, degradability improves, and it is easier to the hydrophilic and hydrophobic of regulation and control polymer material, to can preferably control drug cladding and release rate during being used as pharmaceutical carrier.
Description
Technical field
The present invention relates to a kind of coumarin derivative, that is, 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins
Element further relates to the preparation method and 7- [2- (4- vinyl of 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins
Benzyloxy)-ethyoxyl] the application of -4- methylcoumarins in the synthesis of light stimulus response function polymer material, belong to fining
The organic synthesis field of work intermediate.
Background technology
Cumarin (also known as 1,2- benzopyrones) and its derivative are the compounds of a kind of lactone ring structure, are not only had
The effects that antibacterial, anticoagulation, anti-inflammatory and decompression, and some derivatives also have HIV-resistant activity and antitumor action.In addition,
Cumarin precursor structure chromene itself and unstressed configuration, but the coumarin derivative after substitution, often have good fluorescence
Performance, the high stoke shift of fluorescence quantum yield is big, light stability is good.Therefore, cumarin and its derivative are as excellent glimmering
Optical brightener, laser dye, fluorescence probe are widely used in polymer material, perfume industry, pesticide industry, analysis detection
Equal fields.Cumarin parent is in ultraviolet light λ>Quaternary cyclization occurs under 310nm light conditions at olefinic double bonds unit, realizes that light is handed over
Connection reaction, as ultraviolet light λ<Opposite process can occur again for the four-membered ring generated under 260nm light conditions, i.e. photodissociation crosslinking is anti-
It answers.Using photocrosslinking, solution cross-linked material as nano-carrier, the cladding of drug and light-operated release etc. can be also used for.Profit
With its quick photoreactivity energy to extraneous light stimulus (such as ultraviolet light, near infrared light), synthesis " photoresponse type " intelligence can be designed
Energy polymer, can control its structure by the adjusting to light position, wavelength, intensity and light application time length.Currently, related
The report of benzyl chloride substitution reaction directly occurs with 4- vinyl benzyl chlorides in Hymecromone, but this monomer is deposited
The shortcomings that be synthesis the bad control of polymer material hydrophilic and hydrophobic, be not easy to control during using as pharmaceutical carrier
Drug coats and release rate.
Invention content
In view of the problems of the existing technology, first purpose of the invention is to be the provision of one kind having vinyl benzyl
The coumarin derivative of oxygroup double bond primitive, alkoxy flexible spacer and cumarin photosensitive group, can be used as photosensitive monomer
Applied to the synthesis of light stimulus responsive polymer material, there is good foreground.
Second object of the present invention is to be to provide that a kind of process is simple, reaction condition safety and mild, reaction time
The preparation of the relatively high 7- of short, product easy purification, yield [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins
There is higher purity to remain apparent mass yield advantage for method, the product of synthetic method subsequent processing after purification, fit
For industrial production.
Third object of the present invention is to be to provide 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins
Application of the element in synthesizing light stimulus responsive polymer material can not only improve polymerisation efficiency, and synthesize poly-
Water solubility, the degradability raising of object material are closed, and is easier to the hydrophilic and hydrophobic of regulation and control polymer material, to as drug
Drug cladding and release rate can be preferably controlled during carrier use.
In order to achieve the above technical purposes, the present invention provides a kind of coumarin derivatives, with 1 structure of formula：
Wherein, R C2~C6Alkane chain.
The coumarin derivative of the present invention has the vinyl benzyl oxygroup double bond primitive that may participate in polymerization simultaneously, increases chain length
The flexible alkoxy interval base of degree and there is cumarin photosensitive group, it is organic by homopolymerization or with other to can be used as photosensitive monomer
Monomer is with a wide range of applications by being copolymerized the functional polymer material for obtaining and having light stimulus response.
7- (2- (4- vinyl benzyls oxygroup)-the ethyoxyl) -4- methylcoumarins of the present invention are increased by introducing alkoxy
Chain length, one side polarity become larger, and key is more easily broken off, and activity is got higher, and flexible chain growth is easier to that polymerisation occurs, can
To improve polymerisation efficiency；On the other hand, chain length and polarity are increased by alkoxy, its water solubility is made to increase, is degradable
Property increase, molecular rigidity is stronger, it is easier to regulate and control the hydrophilic and hydrophobic of polymer, to which preferably control polymer material is as medicine
Drug cladding and release rate during object carrier use.
The present invention also provides the preparation methods of coumarin derivative comprising following steps：
Step 1)：Hymecromone and halogenated alcohols compound carry out under Anhydrous potassium carbonate catalytic action
Substitution reaction obtains 7- (2- hydroxyl-oxethyls) -4- methylcoumarins；
The halogenated alcohols compound has 2 structure of formula：
Wherein, X is halogen, R C2~C6Alkane chain；
Step 2)：7- (2- hydroxyl-oxethyls) -4- methylcoumarins, which are catalyzed with 4- vinyl benzyl chlorides in Anhydrous potassium carbonate, to be made
Benzyl chloride substitution reaction is carried out under to get 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins.
Preferred scheme, in step 1), the quality of Anhydrous potassium carbonate be Hymecromone quality 40~
60%.
Preferred scheme, in step 1), the mole of halogenated alcohols compound is Hymecromone mole
1~2 times.
Preferred scheme, in step 1), substitution reaction carries out in n,N-Dimethylformamide solvent, and N, N- dimethyl
The volume mass of formamide and Hymecromone ratio is 10~30mL/g.
Preferred scheme, in step 1), the temperature of substitution reaction is 65~85 DEG C, and the time is 20~24 hours.
Preferred scheme, in step 2), the quality of Anhydrous potassium carbonate is 7- (2- hydroxyl-oxethyls) -4- methylcoumarin quality
The 60~80% of amount.
Preferred scheme, in step 2), the mole of 4- vinyl benzyl chlorides is 7- (2- hydroxyl-oxethyls) -4- methylcoumarins
1~2 times of plain mole.
Preferred scheme, in step 2), benzyl chloride substitution reaction carries out in n,N-Dimethylformamide solvent, and N, N- bis-
The volume mass ratio of methylformamide and 7- (2- hydroxyl-oxethyls) -4- methylcoumarins is 10~30mL/g.
In step 2), bis- (2,6- di-t-butyl -4- aminomethyl phenyls) is added during benzyl chloride substitution reaction in preferred scheme
Pentaerythritol diphosphate is as polymerization inhibitor, the quality of bis- (2,6- di-t-butyl -4- aminomethyl phenyls) pentaerythritol diphosphates
It is the 10~30% of 7- (2- hydroxyl-oxethyls) -4- methylcoumarin quality.Bis- (2,6- di-t-butyl -4- aminomethyl phenyls) seasons penta
Tetrol bisphosphate is mainly used for preventing carbon-carbon double bond that auto polymerization reaction occurs.
Preferred scheme, in step 2), the temperature of benzyl chloride substitution reaction is 65~85 DEG C, and the reaction time is 20~24 small
When.
Preferred scheme, in step 2), benzyl chloride substitution reaction carries out under atmosphere of inert gases.
The present invention also provides the applications of coumarin derivative, are rung as photosensitive function monomer for synthesizing light stimulus
Answer functional polymer material.
Coumarin derivative (7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins) provided by the invention
Preparation method it is as follows：Hymecromone and ethylene bromohyrin are in the presence of catalyst Anhydrous potassium carbonate in fire-bar
It is stirred strongly under part, intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins is obtained by substitution reaction, reaction equation is such as
Under：
7- (2- hydroxyl-oxethyls) -4- methylcoumarins and 4- vinyl benzyl chlorides in the presence of catalyst Anhydrous potassium carbonate
It is stirred strongly under heating condition, target product 7- (2- (4- vinyl benzyls oxygroup)-ethoxies is prepared for by benzyl chloride substitution reaction
Base) -4- methylcoumarins, reaction equation is as follows：
Technical scheme of the present invention is only by two step substitution reactions, using Hymecromone as raw material, quickly
7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins are efficiently synthesized, substitution reaction process is easy to operate, reacts
Time is short, reaction condition is mild, product easy purification, yield are high, by-product is less.It is taken especially by benzyl chloride and hydroxyl
The opposite esterification of generation reaction is easier to make for, and mainly since chlorine atom has stronger electronegativity, is mainly showed in benzyl chloride
For strong electrophilic inductive effect, and it is very weak with the conjugation of benzyl.The method of the present invention is used as using inorganic weak bases potassium carbonate and is tied up
Sour agent and catalyst synthesize 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methyl to be catalyzed Hymecromone
Cumarin, compared with organic base, potassium carbonate is of low cost, is easy to preserve.
The preparation of coumarin derivative 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins of the present invention
Method, including following two step：
First step substitution reaction：Hymecromone and ethylene bromohyrin are in the presence of catalyst Anhydrous potassium carbonate
Intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins are prepared by substitution reaction, preparation process is added into reaction tube
Hymecromone, n,N-Dimethylformamide, Anhydrous potassium carbonate are used rubber stopper tube sealing after ultrasonic disperse, are stirred strongly
It mixes, waits for stable system and after mixing, ethylene bromohyrin is injected in reaction tube dropwise, stirring in a heated condition carries out anti-
It answers；After reaction, filtrate is instilled into Precipitation in ice deionized water, is dried under vacuum to after repeatedly being washed with ice deionized water
Constant weight obtains 7- (2- hydroxyl-oxethyls) -4- methylcoumarins；Wherein, the time of ultrasonic disperse is 10~30 minutes.
Second step benzyl chloride replaces：7- (2- hydroxyl-oxethyls) -4- methylcoumarins and 4- vinyl benzyl chlorides catalyst without
7- [2- (4- vinyl benzyls oxygroup]-ethyoxyl is prepared for by benzyl chloride substitution reaction in the presence of aqueous carbonate potassium) -4- methylcoumarins
Element；7- (2- hydroxyl-oxethyls) -4- methylcoumarins, N,N-dimethylformamide, nothing is added in preparation process into reaction tube
Aqueous carbonate potassium, bis- (2,6- di-t-butyl -4- aminomethyl phenyls) pentaerythritol diphosphates use rubber stopper tube sealing after ultrasonic disperse,
Strong stirring, is passed through inert gas to remove oxygen in reactor, stable system and after mixing is waited for, by 4- vinyl benzyl chlorides
It injects in reaction tube dropwise, is stirred to react in a heated condition, waits for filtering after reaction, filtrate is instilled in ice deionized water
Precipitation, filter cake is washed with sodium hydroxide solution, saturated nacl aqueous solution, deionized water successively after filtering, is dried under vacuum to
Constant weight obtains target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins；Wherein, ultrasonic disperse when
Between be 10~30 minutes；What the atmosphere of inert gases of benzyl chloride substitution reaction was realized as follows：It is added in reaction tube anti-
After answering reagent, freezed-vacuumized repeatedly-inflated with nitrogen or argon gas operation thoroughly to remove the oxygen inside reaction tube and solvent
Gas, the security risk brought due to avoiding 4- vinyl benzyl chlorides that explosion occurs after chemical property is vivaciously mixed with air；Benzyl chloride takes
In generation reaction, 4- vinyl benzyl chlorides should be excessive relative to the dosage of intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins, with
Ensure that the reaction was complete for -4- methylcoumarins by 7- (2- hydroxyl-oxethyls).After benzyl chloride substitution reaction, gained 7- [2- (4- vinyl benzyls
Oxygroup)-ethyoxyl] -4- methylcoumarins first pass through ice deionized water and yellow solid precipitate are precipitated, using the steps such as being filtered, washed
Suddenly.
Compared with the prior art, what technical scheme of the present invention was brought has the beneficial effect that：
(1) technical solution of the present invention is introduced by MOLECULE DESIGN on Hymecromone photosensitive group parent
The alkoxy flexible spacer of polymerizable vinyl benzyl oxygroup double bond primitive and growing chain, the coumarin derivative production of acquisition
Object can be used as photosensitive monomer and be applied to synthesis light stimulus responsive polymer polymer material, have good development prospect.
(2) technical solution of the present invention makes intermediate 7- (2- hydroxyl-oxethyls)-by the dosage of control 4- vinyl benzyl chlorides
The reaction was complete for 4- methylcoumarins, and under the premise of being generated substantially without by-product, mass yield may be up to 91.5% or so, instead
It answers condition safe and mild, there are apparent yield and security advantages, be suitable for industrialized production.
(3) technical scheme of the present invention uses Hymecromone and ethylene bromohyrin in catalyst Carbon Dioxide
In the presence of potassium, intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins are prepared for by substitution reaction.Then 7- (2- hydroxyls
Ethyoxyl) -4- methylcoumarins and 4- vinyl benzyl chlorides pass through benzyl chloride substitution reaction system in the presence of catalyst Anhydrous potassium carbonate
Standby target product 7- [2- (4- vinyl benzyls oxygroup]-ethyoxyl) -4- methylcoumarins.Whole experiment process is only by two
Walk substitution reaction, it is easy to operate, the reaction time is short, product easy purification, yield are relatively high, it avoids and is synthesized using esterification
The defects such as method by-product is more, the reaction time is long, product purity is low.
(4) technical scheme of the present invention is in the Green environmental protection of crude product purification process, and the precipitating reagent used is ice deionization
Water, detergent are followed successively by sodium hydroxide solution, saturated nacl aqueous solution, significantly improve the environment that organic solvent system is brought
Pollution problem significantly increases its adaptive in the industrial production.
(5) 7- (2- (4- vinyl benzyls oxygroup)-ethyoxyl) -4- methylcoumarins of the invention are used for as photosensitive monomer
Synthesizing the relatively existing coumarin derivative of light stimulus responsive polymer material has apparent advantage：By introduce alkoxy come
Increase polarity, key is made more to be easily broken off, and be easier to that polymerisation occurs, polymerisation efficiency can be improved；Pass through ethyoxyl
Increase chain length and polarity, so that its water solubility is increased, degradability increase, molecular rigidity is stronger, it is easier to regulate and control polymer
Hydrophilic and hydrophobic, to preferably control drug cladding during light stimulus responsive polymer material is used as pharmaceutical carrier and release
Rate is put, makes light stimulus responsive polymer material that there is better application prospect.
Description of the drawings
【Fig. 1】For embodiment 1 gained intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins1H NMR figures.
【Fig. 2】For 1 gained target product 7- of embodiment [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins
's1H NMR figures.
【Fig. 3】For poly- (7- [2- (4- vinyl benzyls oxygroup)-the ethyoxyl] -4- methyl of 4 gained random copolymer of embodiment
Cumarin-hydroxyethyl methacrylate-dimethylaminoethyl methacrylate)1H NMR figures.
【Fig. 4】For comparative example 1 gained intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins1H NMR figures.
【Fig. 5】It is fragrant for 2 gained target product 7- of comparative example [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methyl
Legumin1H NMR figures.
Specific implementation mode
Following embodiment is intended to further illustrate the content of present invention, rather than limits the protection model of the claims in the present invention
It encloses.
Embodiment 1
Hymecromone (5g, 28.38mmol), N,N-dimethylformamide are added into reaction tube
(50mL) and Anhydrous potassium carbonate (3g), ultrasonic disperse use rubber stopper tube sealing after ten minutes.Reaction tube is stirred strongly at 85 DEG C,
It waits for stable system and after mixing, ethylene bromohyrin (2.84ml, 40mmol) is injected into reaction tube dropwise with disposable syringe
In, and be stirred to react strongly 20 hours.It filters after reaction, then filtrate is instilled in ice deionized water, there is white solid
It is precipitated, vacuum to constant weight obtains intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins after repeatedly being washed with ice deionized water.
7- (2- hydroxyl-oxethyls) -4- methylcoumarins (1.1g, 5mmol), N, N- dimethyl methyls are added into reaction tube
Amide (20ml), bis- (2,6- di-t-butyl -4- aminomethyl phenyls) pentaerythritol diphosphates (0.11g) and Anhydrous potassium carbonate
Reaction tube, is hereafter placed at 65 DEG C and stirs strongly, be passed through High Purity Nitrogen by (0.83g), ultrasonic disperse rubber stopper tube sealing after ten minutes
Gas is occurred with removing the oxygen in reaction system after preventing 4- vinyl benzyl chlorides from vivaciously being mixed with air because of chemical property for 20 minutes
Explosion.It waits for stable system and after mixing, is noted 4- vinyl benzyl chlorides (0.853ml, 6mmol) dropwise with disposable syringe
Enter in reaction tube, is stirred strongly at 65 DEG C 24 hours.It filters, then instills filtrate in ice deionized water after reaction,
Have yellow solid precipitate precipitation, the filter cake sodium hydroxide solution of a concentration of 40g/L, saturated nacl aqueous solution after filtering, go from
Sub- water washing is dried under vacuum to constant weight and obtains target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methyl to neutrality
Cumarin.
Embodiment 2
First intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins are obtained according to the first step substitution reaction of embodiment 1.
7- (2- hydroxyl-oxethyls) -4- methylcoumarins (1.1g, 5mmol), N, N- dimethyl methyls are added into reaction tube
Amide (20ml), bis- (2,6- di-t-butyl -4- aminomethyl phenyls) pentaerythritol diphosphates (0.11g) and Anhydrous potassium carbonate
Reaction tube, is hereafter placed at 65 DEG C and stirs strongly, be passed through High Purity Nitrogen by (0.83g), ultrasonic disperse rubber stopper tube sealing after ten minutes
Gas is occurred with removing the oxygen in reaction system after preventing 4- vinyl benzyl chlorides from vivaciously being mixed with air because of chemical property for 20 minutes
Explosion.It waits for stable system and after mixing, is noted 4- vinyl benzyl chlorides (1.137ml, 8mmol) dropwise with disposable syringe
Enter in reaction tube, is stirred strongly at 65 DEG C 24 hours.It filters, then instills filtrate in ice deionized water after reaction,
Have yellow solid precipitate precipitation, the filter cake sodium hydroxide solution of a concentration of 40g/L, saturated nacl aqueous solution after filtering, go from
Sub- water washing is dried under vacuum to constant weight and obtains target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methyl to neutrality
Cumarin.
Embodiment 3
First intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins are obtained according to the first step substitution reaction of embodiment 1.
7- (2- hydroxyl-oxethyls) -4- methylcoumarins (1.1g, 5mmol), N, N- dimethyl methyls are added into reaction tube
Amide (20ml), bis- (2,6- di-t-butyl -4- aminomethyl phenyls) pentaerythritol diphosphates (0.11g) and Anhydrous potassium carbonate
Reaction tube, is hereafter placed at 65 DEG C and stirs strongly, be passed through High Purity Nitrogen by (0.83g), ultrasonic disperse rubber stopper tube sealing after ten minutes
Gas is occurred with removing the oxygen in reaction system after preventing 4- vinyl benzyl chlorides from vivaciously being mixed with air because of chemical property for 20 minutes
Explosion.It waits for stable system and after mixing, is noted 4- vinyl benzyl chlorides (1.42ml, 10mmol) dropwise with disposable syringe
Enter in reaction tube, is stirred strongly at 65 DEG C 24 hours.It filters, then instills filtrate in ice deionized water after reaction,
Have yellow solid precipitate precipitation, the filter cake sodium hydroxide solution of a concentration of 40g/L, saturated nacl aqueous solution after filtering, go from
Sub- water washing is dried under vacuum to constant weight and obtains target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methyl to neutrality
Cumarin.
Embodiment 4 (copolymerization process of synthesized target product and other organic monomers)
Into reaction tube be added 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins (1.464g,
4mmol), hydroxyethyl methacrylate (0.52g, 4mmol), dimethylaminoethyl methacrylate (1.1g, 7mmol) are dissolved in
In 15ml dioxane, initiator azodiisobutyronitrile (0.074g, 0.45mmol), ultrasonic disperse rubber stopper after ten minutes is added
Tube sealing, it is strong to stir, high pure nitrogen is passed through 20 minutes to remove the oxygen in reaction system, and it is small to stir 24 strongly at 65 DEG C
When.N-hexane washed product is used in combination three times in mixed liquor Precipitation in n-hexane after reaction, and products therefrom is placed in vacuum
Drying to constant weight obtains poly- (7- [2- (4- vinyl benzyls oxygroup)-the ethyoxyl] -4- methylcoumarins-methyl-prop of random copolymer
Olefin(e) acid hydroxyl ethyl ester-dimethylaminoethyl methacrylate), mass yield 61%.
Comparative example 1
Be added into reaction tube Hymecromone (5g, 28.38mmol), absolute ethyl alcohol (50mL) and 3g without
Aqueous carbonate potassium, ultrasonic disperse use rubber stopper tube sealing after ten minutes.Reaction tube is stirred strongly at 85 DEG C, stable system is waited for and mixes
After closing uniformly, ethylene bromohyrin (2.84ml, 40mmol) is injected in reaction tube dropwise with disposable syringe, it is strong at 85 DEG C
It is stirred to react 20 hours.It filters after reaction, then filtrate is instilled in ice deionized water, has white solid precipitation, repeatedly
Vacuum to constant weight obtains intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins after being washed with ice deionized water.
Then it carries out second step benzyl chloride substitution reaction according to embodiment 1 and obtains target product 7- [2- (4- vinyl benzyloxies
Base)-ethyoxyl] -4- methylcoumarins.
Comparative example 2
First intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins are obtained according to the first step substitution reaction of embodiment 1.
7- (2- hydroxyl-oxethyls) -4- methylcoumarins (1.1g, 5mmol), N, N- dimethyl methyls are added into reaction tube
Amide (20ml), bis- (2,6- di-t-butyl -4- aminomethyl phenyls) pentaerythritol diphosphates (0.11g), potassium hydroxide (0.83g)
With polyethylene glycol (0.11g), hereafter reaction tube is placed at 65 DEG C and stirs strongly by ultrasonic disperse rubber stopper tube sealing after ten minutes,
Be passed through high pure nitrogen 20 minutes to remove the oxygen in reaction system, prevent 4- vinyl benzyl chlorides because of chemical property vivaciously and air
It explodes after mixing.Wait for stable system and after mixing, with disposable syringe by 4- vinyl benzyl chlorides (1.42ml,
It 10mmol) injects in reaction tube, is stirred strongly at 65 DEG C 24 hours dropwise.It filters, then instills filtrate after reaction
In ice deionized water, there is yellow solid precipitate precipitation, the sodium hydroxide solution of a concentration of 40g/L of filter cake, saturation chlorine after filtering
Change sodium solution, deionized water are washed to neutrality, are dried under vacuum to constant weight and are obtained target product 7- [2- (4- vinyl benzyls oxygroup)-
Ethyoxyl] -4- methylcoumarins.
The characterization of sample and test：
Structural characterization：With the AVANCE III 400MHz total digitalization superconduction nuclear magnetic resonance spectrometers of Brooker,Switzerland company
The structure of products therefrom is characterized.In test process, intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins use deuterium
It is used as solvent, target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins for dimethyl sulfoxide (DMSO) (DMSO)
Use deuterochloroform (CDCl3) solvent, target product is used as to use deuterated chlorine with the copolymer that other organic monomers are copolymerized
Imitative (CDCl3) it is used as solvent.
In order to confirm the structure of intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins, embodiment 1 and comparison are implemented
1 intermediate of example carries out1H NMR characterizations, as a result as shown in Figure 1 and Figure 4.From Fig. 1 and Fig. 4：In 4.93~4.95ppm
There is hydroxyl peak in (1H, 1), and 3.69~3.73ppm (2H, 2) and 4.10~4.12ppm (2H, 3) methylene peak occur, illustrate reality
It is title intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins to apply example 1 and 1 product of comparative example.
In order to confirm the structure of target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins, to reality
It applies example 1 and 2 target product of comparative example carries out1H NMR characterizations, as a result as shown in Figure 2 and Figure 5.In 5.12~5.16ppm
There is methylene peak in (2H, 5), and ethylene base peak nearby occur in 5.22~5.29ppm and 5.72~5.80ppm (2H, 1), with
And nearby there is phenyl ring skeleton peak in 7.5ppm, illustrates that embodiment 1 and 2 product of comparative example are target product 7- [2- (4- second
Alkenyl benzyloxy)-ethyoxyl] -4- methylcoumarins.
In order to confirm poly- (7- [2- (4- vinyl benzyls oxygroup)-the ethyoxyl] -4- methylcoumarins-methyl of random copolymer
Hydroxy-ethyl acrylate-dimethylaminoethyl methacrylate) structure, 4 gained polymerizate of embodiment is carried out1H NMR
Characterization, the results are shown in Figure 3.As seen from the figure：There is 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl]-in 6.17~6.72ppm
Proton peak in 4- methylcoumarin units on phenyl ring；Occurs methyl in hydroxyethyl methacrylate unit near ppm
Proton peak, and also the position of 2.21~2.46ppm goes out the hydrogen atom in hydroxyethyl methacrylate unit on hydroxyl on spectrogram
It is existing；The proton peak for occurring methyl in dimethylaminoethyl methacrylate unit near 2.76~3.22ppm illustrates to implement
4 product of example is poly- (7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins-hydroxyethyl methacrylate-methyl
Dimethylaminoethyl acrylate).This shows target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- obtained by the present invention
Methylcoumarin can carry out combined polymerization with other organic monomers, to obtain the copolymer with photosensitive property.
The mass yield for finally comparing these experiments, as can be seen from Table 1, with pair for using absolute ethyl alcohol to make solvent
It is compared than embodiment 1, the embodiment 1 for making solvent using n,N-Dimethylformamide greatly improves the conversion of substitution reaction
Rate, intermediate mass yield are up to 94.3%, to improve the gross mass yield of target product.This is because 7- hydroxyl -4- first
Solubility property of the butylcoumariii in n,N-Dimethylformamide is fabulous, can only but be slightly soluble in absolute ethyl alcohol.It can be seen by table 2
Go out, from embodiment 1 to embodiment 3, as 4- vinyl benzyl chloride dosages increase, target product mass yield increases, especially
It is that the mass yield of embodiment 3 is up to 91.5%, this is because 4- vinyl benzyl chlorides are excessive, it is ensured that 7- (2- '-hydroxyethoxies
Base) the reaction was complete for -4- methylcoumarins.Meanwhile with 2 phase of comparative example that uses potassium hydroxide and polyethylene glycol to make catalyst
Than the embodiment 3 for making catalyst using Anhydrous potassium carbonate has higher benzyl chloride substitution reaction conversion ratio, this is because hydroxide
Potash is stronger than Anhydrous potassium carbonate, and alkalinity can cause by force benzyl chloride substitution reaction to be difficult to obtain good control very much.
The mass yield of 1 embodiment of table and intermediate 7- (2- hydroxyl-oxethyls) -4- methylcoumarins in comparative example
2 embodiment of table and target product 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methyl in comparative example are fragrant
The mass yield of legumin
Claims (10)
1. a kind of coumarin derivative, it is characterised in that：With 1 structure of formula：
Wherein, R C2~C6Alkane chain.
2. the preparation method of coumarin derivative described in claim 1, it is characterised in that：Include the following steps：
Step 1)：Hymecromone and halogenated alcohols compound are replaced under Anhydrous potassium carbonate catalytic action
Reaction, obtains 7- (2- hydroxyl-oxethyls) -4- methylcoumarins；
The halogenated alcohols compound has 2 structure of formula：
Wherein, X is halogen, R C2~C6Alkane chain；
Step 2)：7- (2- hydroxyl-oxethyls) -4- methylcoumarins are with 4- vinyl benzyl chlorides under Anhydrous potassium carbonate catalytic action
Benzyl chloride substitution reaction is carried out to get 7- [2- (4- vinyl benzyls oxygroup)-ethyoxyl] -4- methylcoumarins.
3. the preparation method of coumarin derivative according to claim 2, it is characterised in that：
In step 1), the quality of Anhydrous potassium carbonate is the 40~60% of Hymecromone quality；
In step 1), the mole of halogenated alcohols compound is 1~2 times of Hymecromone mole.
4. the preparation method of coumarin derivative according to claim 2, it is characterised in that：In step 1), substitution reaction
It is carried out in n,N-Dimethylformamide solvent, and the volume matter of n,N-Dimethylformamide and Hymecromone
Amount is than being 10~30mL/g.
5. according to the preparation method of Claims 1 to 4 any one of them coumarin derivative, it is characterised in that：In step 1),
The temperature of substitution reaction is 65~85 DEG C, and the time is 20~24 hours.
6. the preparation method of coumarin derivative according to claim 1, it is characterised in that：
In step 2), the quality of Anhydrous potassium carbonate is the 60~80% of 7- (2- hydroxyl-oxethyls) -4- methylcoumarin quality；
In step 2), the mole of 4- vinyl benzyl chlorides is the 1~2 of 7- (2- hydroxyl-oxethyls) -4- methylcoumarin moles
Times.
7. the preparation method of coumarin derivative according to claim 1, it is characterised in that：In step 2), benzyl chloride substitution
Reaction carries out in n,N-Dimethylformamide solvent, and n,N-Dimethylformamide and 7- (2- hydroxyl-oxethyls) -4- methyl
The volume mass ratio of cumarin is 10~30mL/g.
8. the preparation method of coumarin derivative according to claim 1, it is characterised in that：In step 2), benzyl chloride substitution
Bis- (2,6- di-t-butyl -4- aminomethyl phenyls) pentaerythritol diphosphates are added in reaction process as polymerization inhibitor, bis- (2,6- bis-
Tertiary butyl -4- aminomethyl phenyls) quality of pentaerythritol diphosphate is 7- (2- hydroxyl-oxethyls) -4- methylcoumarin quality
10~30%.
9. according to claim 1, the preparation method of 6~8 any one of them coumarin derivatives, it is characterised in that：Step 2)
In, benzyl chloride substitution reaction carries out under an inert atmosphere, and the temperature of reaction is 65~85 DEG C, and the time is 20~24 hours.
10. the application of coumarin derivative described in claim 1, it is characterised in that：As photosensitive function monomer for synthesizing
Light stimulus response function polymer material.
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